While not technically a research result, many studies are sited in this extensive overview of using topical sensitizers to treat alopecia areata. If you are interested in this form of treatment you would be well advised to read this article in it's entirety.
This was originally posted on the 29th of September, 2004 by Amy J. McMichael & Robert L. Henderson, Jr.
 We again give mad props to the wonderful Medline website.
Abstract
Though many therapies exist for alopecia areata, one of the most unique is topical sensitization. By altering the pathogenic inflammatory response with few side effects, sensitizers offer an attractive treatment option for many patients with alopecia areata, including those who have previously failed more traditional treatments and those who have extensive disease.
Introduction
Alopecia areata (AA) is an autoimmune disease of the hair follicle resulting in patchy or total hair loss from any area on the body. Although many forms of alopecia exist, alopecia areata is distinctive for its circular, nonscarring involvement of the scalp (Hordinsky, 2001). While AA is seen throughout all populations with an equal incidence in men and women (Muller & Winkelmann, 1963), it is more common in younger ages. An estimated 60% of those who develop AA do so before the age of 20 years (Price, 1991).
Histologically, inflammation surrounds the follicular root, thus inducing affected hairs to transition into the falling out phase (telogen phase) (Whiting, 1995). Involved hairs that do not fall out completely have a characteristic exclamation point appearance as they taper towards the base and can frequently be found at the edges of active lesions. The involvement can be so widespread as to involve the entire scalp (alopecia totalis) or entire body (alopecia universalis).
While the hair loss of AA itself is not usually symptomatic, psychosocial effects of the hair loss are often significant. Another important caveat regarding AA is the common association with other autoimmune diseases. Of these, thyroid disease and vitiligo are the most common (Muller & Winkelmann, 1963).
Therapy for AA is primarily directed at halting the underlying inflammation
Therapy for AA is primarily directed at halting the underlying inflammation 
. Traditional therapies for alopecia areata include topical, intralesional, and, rarely, systemic corticosteroids as well as PUVA, minoxidil, and anthralin (Madani & Shapiro, 2000). More recent treatments include imiquimod (Skinner, 2003) and topical sensitizers. Corticosteroids are probably the most effective at decreasing the inflammation but carry significant risks for side effects, particularly if used systemically. Topical and intralesional corticosteroids are usually used as first-line treatments for patchy disease. Treatment of extensive AA is far more challenging. For instance, intralesional corticosteroids are often too painful for treatment of the entire scalp.
Of the other treatments available for AA, topical sensitizers are one of the most unique and include dinitrochlorobenzene (DNCB), squaric acid dibutylester (SADBE), and diphencyprone (DPCP) (Madani & Shapiro, 2000). In this review, the unique immunomodulatory functions of topical sensitizers in the treatment of AA will be discussed, and the mechanisms of the treatment, efficacy, and potential side effects of this treatment reviewed.
Immunology of Topical Sensitizers
Sensitizers include any chemical for which the body develops immunity when exposed. Upon subsequent exposure, an inflammatory response is mounted by the immune system to fight off the chemical. Sensitizers can therefore include a wide range of chemicals and are not necessarily limited to those used in medical therapeutics. Perhaps one of the best known sensitizers is urushiol which is found in poison ivy and poison oak species. Whereas urushiol has little utility in medical therapeutics, other sensitizers do have certain properties that allow their use in treating dermatologic conditions such as AA.
Topical sensitization for treating AA relies on four characteristics of the sensitizer for efficacy: predictable immunomodulation (sensitization of the immune system), absence from the natural environment, lack of cross-reactivity with other substances, and, of course, safety. The absence of the sensitizer from the natural environment is important, or the sensitized individual may experience contact allergy from exposure during routine daily life activities.
Many theories exist for the mechanism of efficacy of sensitizers in AA, and research is lacking to validate them. However, one of the more popular views is that they redirect the inflammatory response in AA away from the hair follicle and direct it towards the exogenous chemical sensitizer (Happle, 1980). But the true mechanism is likely not so simplistic and cannot explain the regrowth that is sometimes observed at distant sites or on opposite sides from sensitizer application (castling phenomenon) suggesting a systemic action (Micali, Cicero, Nasca, & Sapuppo, 1996).
Patient Selection
The best candidates for topical sensitizer treatment include those with severe cases of AA, such as having greater than 50% total scalp involvement with large patches or alopecia totalis. The treatment avoids injections, which is particularly attractive when treating children, offers an alternative to corticosteroids, and offers additional hope after several other standard treatments have failed. Clinical judgment must be exercised for each case since the treatment may be too irritating in patients with atopic dermatitis or those who have easily irritated skin. In patients with little reaction to allergens, sensitizers may not work at all. In patients with small areas of AA involvement, sensitizers may be too difficult to apply through the surrounding hair and are usually unsatisfactory for those who desire fast results. Treatment will also require patients who can followup regularly and can follow complex instructions for self-application (if self-treatment is recommended).
Overall, topical sensitizers are well-tolerated and not time consuming.
Overall, topical sensitizers are well-tolerated and not time consuming.
It is best to not begin treatment prior to an important social event in case a fulminant dermatitis results. Topical corticosteroids and oral antihistamines can be used should such a reaction ensue. It is best to supply samples or a prescription of such treatments when beginning so the patient can be prepared for a severe dermatitis.
Thorough patient education should be addressed and will only increase appropriate compliance and treatment response. Providing a patient handout describing what the medication is and what to expect is beneficial. Since no topical sensitizer is FDA approved, this fact should be openly discussed in the beginning of treatment.
Selecting a Sensitizer
DNCB was the earliest used topical sensitizer. However, it is mutagenic in the Ames test (Kratka, Goerz, & Vizethum, 1979; Summer & Goggelmann, 1980). Though no evidence of carcinogenicity has been demonstrated in treated patients, many now avoid its use for contact sensitivity.
SADBE, in contrast, is not mutagenic by the Ames test nor has cell transformation been demonstrated in vitro. When the mutagenic potential for DNCB became known, SADBE became the great hope and is currently the most used sensitizer in the United States. However, it is unstable in the acetone solutions in which it is prepared and requires refrigeration to maintain potency. Additionally, it is the most expensive topical sensitizer.
DPCP, likewise, is not mutagenic and is preferred in the United Kingdom and Canada. It is not expensive and comes in UV opaque bottles with a shelf-life of approximately 6 months.
Application Methods
Once topical sensitization has been appropriately selected for treatment of AA, the patient must initially be sensitized to the chemical. In our clinics, SADBE is used and sensitization begins with a 2% solution in acetone applied to a 10 to 16 cm2 area on exposed skin. Usually the side of the scalp suffices, but the buttock may serve as an alternative. Using a cotton-tipped applicator dipped twice in the solution provides adequate exposure. As the acetone solvent evaporates quickly, the residual sensitizer is not visible. Following application, the sensitized area should not be washed for 24 hours.
Though rarely used as a self-treatment, we use SADBE in this manner because the distance patients travel to our clinic precludes weekly returns. Self-treatments can begin 2 weeks following sensitization with 0.001% to 0.1% solutions, again applied with a cotton-tipped applicator to the entire affected area. Patients should be reminded to keep the solution refrigerated. Regimens can then consist of every other day to once weekly applications. We usually begin a regimen of 1 to 2 times a week and allow increasing or decreasing the frequency based on the reaction. The strength of solution used can also be titrated to pruritus at subsequent followup visits allowing 4 to 6 months between dosing changes. We use solutions of 0.0001%, 0.001%, 0.01%, 0.1%, 1%, 2%, and 4%. For all the sensitizers, inducing a clinically evident allergic response appears necessary, but not a fulminant dermatitis. Regrowth is usually evident by week 18 (Hull, Cunliffe, & Norris, 1990).
Efficacy
Controlled studies demonstrating conclusive efficacy of all the sensitizers in alopecia areata are lacking. A retrospective chart review in our clinics from 1996 through 1999 demonstrated a 33% cosmetically acceptable or total regrowth in responders to SADBE (Pardasani, Turner, & McMichael, 2001). Micali et al. (1996) demonstrated an 80% rate of regrowth in less-severe forms and 49% in more severe cases with SADBE. DNCB was significantly effective in a group of 90 patients with alopecia areata (Happle, Cebulla, & Echternacht-Happle, 1978), with 80 (89%) regrowing hair exclusively or thicker on the treated side and 72 (80%) having persistent responses. Other reports have shown similar efficacy for all the sensitizers.
Despite an appropriate selection of good candidates, topical sensitization proves ineffective in some cases. A reported 1% to 2% of patients cannot be sensitized (Van der Steen & Happle, 1993), and successful sensitization can be lost. Tolerance is reported in 10.8%, though concomitant oral cimetidine may avert the loss (Daman & Rosenberg, 1977).
Negative prognostic factors for response to topical sensitization include duration and extent of disease, younger age of onset, family history of alopecia areata, and nail changes evident on clinical exam (Iijima & Osuka, 1997; Van der Steen, Van Baar, Happle, Boezeman, & Perret, 1991; Weise, Kretzschmar, John, & Hamm, 1996). However, an early development of dermatitis to the agent is viewed as a positive sign in all cases.
Conclusion
Topical sensitization offers a unique therapeutic alternative to traditional treatments for AA. It also offers many advantages over other treatments in extensive AA such as alopecia totalis. Of the three currently used sensitizers in medical therapeutics, SADBE is favored in the United States and adequately meets the four requirements for efficacy. It predictably induces immunity in the majority of patients, is not present in the natural environment, lacks cross-reactivity with other substances, and has demonstrated no safety concerns. Patients using topical sensitizers must be motivated and able to follow complex treatment regimens. Though conclusive trials have not been performed assessing efficacy, anecdotal evidence and case series point to topical sensitization as an attractive and effective treatment for alopecia areata.
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